Search Results (557)

Plant transformation efficiency is highly dependent on species, individual genotypes, and tissue types. In maize, immature embryos are regularly used for transformation. The process relies heavily on callus development, as it is intricately associated with somatic embryogenesis and subsequent plant regeneration, both of which directly affect transformation efficiency. Immature embryos of the segregation progeny derived from the two inbred parents, a transformation-amenable line A188 and a recalcitrant line B73, can be cultured to form two primary callus types: Type I and Type II. The Type II callus grows faster and is a favorable type for regeneration. Here, Type I and II calli from the B73xA188 F2 population were genotyped by Genotyping-By-Sequencing (GBS). Quantitative trait locus (QTL) analysis of the callus type identified QTLs at chromosomes 2, 5, 6, 8, and 9. The result was largely supported by the bulk segregant RNA-seq (BSR-seq) genetic analysis using RNA from separately pooled Type I and II calli. Both analyses revealed that an allele of A188 on chromosome 6 and B73 alleles on chromosomes 2, 5, 8, and 9 promoted the formation of the Type II callus. Differentially expressed genes (DEGs) between the Type II and I F2 calli were also identified. In addition, the A188 calli developed from the same immature embryos often exhibit heterogeneous morphology, including the fast- and slow-growing callus sectors. The transcriptional comparison between the two sectors was performed to identify DEGs. Both sets of DEGs were enriched in genes involved in cell-wall organization and wax biosynthesis pathways. Full article

Low light intensity is a major abiotic stress that severely affects rice yields, particularly in India and Southeast Asia, causing yield reductions of 35–40% during the wet season compared to the dry season. Tolerant rice genotypes exhibit adaptive changes at anatomical, physiological, biochemical, and molecular levels under low-light stress, enabling higher yields compared to susceptible varieties. Our study identified 20 novel QTLs associated with grain yields and nine related traits under low-light and control (normal)-light conditions, using a recombinant inbred line (RIL) population derived from the cross between the low-light-tolerant variety Swarnaprabha and the low-light-susceptible variety IR8. Across the Kharif seasons of 2019 and 2021, 33 stable QTLs were identified, with 11, 13, and 9 QTLs specific to low-light, normal-light, and both conditions, respectively. Of these, Swarnaprabha contributed 28 QTLs, while five were contributed by IR8. Notably, the study identified 11 and 9 novel QTLs under low-light and both conditions, respectively. Three hotspot regions on chromosomes 1, 4, and 8 were identified. These regions harbored 10 novel QTLs and revealed twenty candidate genes, out of which three key hub genes, OsAUX1, OsSBDCP1, and OsNPF5.16, were identified. These hub genes are involved in hormone signaling, starch metabolism, and nitrogen metabolism, respectively. A comprehensive expression analysis of these genes indicated that they are linked to low-light tolerance, offering deeper insights into the genetic and molecular mechanisms underlying low-light resilience. These findings provide valuable genomic resources and potential markers for breeding programs for improving rice productivity under low-light conditions. Full article

Background/Objectives: The Chinese dwarf cherry (Cerasus humilis) is an endemic shrub fruit tree species in China. Its fruit is flavorful, nutrient-rich, and has considerable research and utilization potential. However, most currently cultivated varieties of C. humilis are highly acidic and primarily used for processing. Consumer-preferred, low-acid, fresh-eating varieties are scarce, limiting industrial development. We used 208 F₁ individuals derived from a cross between high-acid “Nongda 4” and the low-acid “DS-1”. Methods: Restriction site-associated DNA sequencing (RAD-seq) was used to develop single-nucleotide polymorphism (SNP) markers and construct a high-density genetic linkage map. Using two years of fruit titratable acidity phenotypic data, quantitative trait locus (QTL) mapping and candidate gene screening were performed. Results: The genetic map contained 2491 SNP markers, assigned to eight linkage groups. The total genetic distance was 672.71 cm, with an average distance of 0.27 cm between markers, indicating high map quality. QTL mapping identified 18 loci associated with fruit titratable acidity, including 11 major-effect QTLs (logarithm of odds, LOD ≥ 3.5). These major-effect QTLs were concentrated on linkage groups LG2 and LG5, with an explained phenotypic variation of 8.6–31.13%. Two candidate genes were identified within QTL intervals: phosphoester phosphatase and MATE transmembrane transporter. The phosphatase gene’s expression showed a strong correlation with titratable acid content (p < 0.01, correlation coefficient 0.93), suggesting that it plays an important role regulating fruit acidity in C. humilis. Conclusions: This study supports marker-assisted breeding of low-acid, fresh-eating varieties, aiding commercial promotion of C. humilis. Full article

Migraine is a complex neurological disorder that severely compromises quality of life. Current therapies remain inadequate, creating an urgent need for precision medicine approaches. To bridge this gap, we integrated genome-wide association studies (GWASs) and multi-tissue expression quantitative trait loci (eQTL) data. Using Mendelian randomization (SMR/HEIDI) to identify putatively causal genes, followed by colocalization analysis, protein–protein interaction networks, and gene enrichment, we prioritized druggable targets. Phenome-wide association studies (PheWASs) further assessed their potential safety profiles. We identified 31 migraine-associated genes in whole blood, 20 in brain tissue, and 9 genes shared by both whole blood and brain regions. Among 13 druggable genes identified from the DGIdb and supporting literature, 10 passed colocalization validation. Eight genes (TGFB3, CHRNB1, BACE2, THRA, NCOR2, NR1D1, CHD4, REV3L) showed interactions with known drug targets, enabling the computational prediction of 41 potential repurposable drugs. Based on target druggability, PPI (protein–protein interaction) and favorable PheWAS profiles, NR1D1, THRA, NCOR2, and CHD4 are prioritized for drug development. Additionally, MICU1, UFL1, LY6G5C, and PPP1CC emerged as novel pathophysiological factors. This study establishes a multi-omics framework for precision migraine therapy, translating genetic insights into clinically actionable targets. Full article

Background/Objectives: Prepulse inhibition (PPI) is a robust, reproducible phenotype associated with schizophrenia and other psychiatric disorders. This study was carried out to identify gene(s) influencing PPI. Methods: We performed Quantitative Trait Locus (QTL) analysis of PPI in 59 strains from the BXD recombinant inbred (BXD RI) mouse family and used a 2-LOD region for candidate gene identification. Genes significantly correlated with the candidate gene were identified based on genetic, partial, and literature correlation, and were further studied through gene enrichment and protein–protein interaction analyses. Phenome-wide association study (PheWAS) and differential expression analyses of the candidate gene were performed using human data. Results: We identified one significant (GN Trait 11428) and two suggestive male-specific QTLs (GN Traits 11426 and 11427) on Chromosome 19 between 27 and 36 Mb with peak LRS values of 19.2 (−logP = 4.2), 14.4 (−logP = 3.1), and 13.3 (−logP = 2.9), respectively. Atad1, ATPase family, AAA domain containing 1 was identified as the strongest candidate for the male-specific PPI loci. Atad1 expression in BXDs is strongly cis-modulated in the nucleus accumbens (NAc, LRS = 26.5 (−logP = 5.7). Many of the Atad1-correlated genes in the NAc were enriched in neurotransmission-related categories. Protein–protein interaction analysis suggested that ATAD1 functions through its direct partners, GRIA2 and ASNA1. PheWAS revealed significant associations between Atad1 and psychiatric traits, including schizophrenia. Analysis of a human RNA-seq dataset revealed differential expression of Atad1 between schizophrenia patients and the control group. Conclusions: Collectively, our analyses support Atad1 as a potential candidate gene for PPI and suggest that this gene should be further investigated for its involvement in psychiatric disorders. Full article

As nutrient allocation trade-offs occur between reproductive and vegetative development in crops, optimizing their partitioning holds promise for improving agricultural productivity and quality. Herein, we characterize the phenotypic diversity of the fruitfulness trait and identify associated genes in tea plants (Camellia sinensis). Over three consecutive years, we monitored the fruitfulness of an F₁ hybrid population (n = 206) derived from crosses of ‘Emei Wenchun’ and ‘Chuanmu 217’. A marked variation was observed in the yield of individual plants, ranging from complete sterility (zero fruits) to exceptionally high fertility (1612 fruits). Using the high-resolution genetic linkage map and the fruitfulness data, we identified a stable major QTL designated as qFN5. To fine-map the underlying gene(s), artificial pollination experiments were conducted with extreme phenotype individuals (with the highest vs. lowest fruit numbers). Bulked segregant RNA sequencing (BSR-Seq) with ovules collected at two and seven days post-pollination (DPP) identified the genomic intervals that exhibit a high degree of overlap with qFN5. Analysis of expression dynamics combined with functional genomics data revealed a prominent candidate gene, CsETR2 (TGY048509), which encodes an ethylene receptor protein. When CsETR2 was overexpressed in Arabidopsis thaliana, the transgenic lines exhibited significantly decreased reproductive performance relative to the wild-type plants. Relative to the wild type, the transgenic lines exhibited a significant decline in several key traits: the number of effective panicles decreased by 72.5%, the seed setting rate dropped by 67.7%, and the silique length shortened by 38%. These findings demonstrate its role in regulating plant fruitfulness. Furthermore, yeast one-hybrid and dual-luciferase assays verified that CsMYB15 (TGY110225) directly binds to the CsETR2 promoter, thus repressing its transcription. In summary, our findings expand the understanding of genetic regulation underlying fruitfulness in tea plants and provide candidate target loci for breeding. Full article

Allele-specific expression (ASE) reflects the unequal expression of the parental alleles and can imply functional variants in cis-regulatory elements. The conventional ASE detection methods often depend on the presence of heterozygous variants in transcripts or sequencing a large number of individuals, both of which are often limited. In this study, we present a family-based strategy for detecting ASE and potential cis-regulatory elements utilizing both RNA-seq and whole-genome sequencing (WGS) from a pedigree. Using a rabbit family consisting of two divergent parents and their eight offspring, we identified 913 ASE genes by analyzing inheritance patterns of gene expression levels. Expression was classified into three levels—high, medium, and low—and used to define seven distinct expression groups across the family (e.g., H_L: high in the mother, low in the father, and intermediate in the offspring). Many ASE genes lacked heterozygous exonic variants, and inference was achieved via RNA read count patterns. We also pinpointed conserved transcription factor binding sites (TFBS) with sequence variants showing similar inherited genotypic patterns (e.g., AAxBB), suggesting their regulatory roles as eQTLs. Differential gene expression (DEG) analysis between the parents highlighted some candidate genes related to meat production and quality traits. Our findings show that the family-based method using RNA-seq and WGS data is promising for exploring ASE and mapping possible eQTLs. Full article

Seed oil and protein contents are critical agronomic traits that determine soybean quality. However, the key loci and corresponding genes controlling these quality traits remain to be elucidated. Here, we performed bulked segregant analysis by sequencing (BSA-seq) using an F4 population derived from a cross between the cultivars Heinong 35 (HN35) and Dengke 3 (DK3). A major soybean oil and protein quantitative trait locus (QTL) designated as q-OP18 was identified on chromosome 18, and the sugar transporter gene GmSWEET46 was further cloned. Haplotype analysis revealed that a single-nucleotide polymorphism (SNP) in the sixth exon of GmSWEET46 results in an amino acid change between HN35 and DK3 and is associated with seed oil and protein content, suggesting its important role in determining seed quality in soybean. GmSWEET46 is expressed during the early stages of seed and pod development and localizes to the plasma membrane, indicating its potential function as a sugar transporter. Further studies demonstrated that GmSWEET46 can regulate seed protein content, oil content, and seed size in Arabidopsis and soybean. Collectively, this study provides a novel locus and gene for regulating soybean seed traits and offers valuable resources for the breeding of high-quality and high-yielding soybean cultivars. Full article

Background: Breast ductal carcinoma in situ (DCIS), a common precursor of breast cancer, has poorly understood susceptible driver genes. This study aimed to identify genes influencing DCIS progression by integrating Mendelian randomization (MR) and Gene Expression Omnibus (GEO) datasets. Methods: The GEO database was searched for DCIS-related datasets to extract differentially expressed genes (DEGs). MR was employed to find exposure single-nucleotide polymorphisms (SNPs) of expression quantitative trait locus (eQTL) gene expression from Genome-Wide Association Study database (GWAS) (IEU openGWAS project). DCIS was designated as the outcome variable. The intersection of genes was used for GO, KEGG and CIBERSORT analyses. The functional validation of selected DEGs was performed using Transwell invasion assays. Results: Four datasets (GSE7782, GSE16873, GSE21422, and GSE59246) and 19,943 eQTL exposure data were obtained from GEO and the IEU openGWAS project, respectively. By intersecting DEGs, 13 genes (LGALS8, PTPN12, YTHDC2, RNGTT, CYB5R2, KLHDC4, APOBEC3G, GPX3, RASA3, TSPAN4, MAPKAPK3, ZFP37, and RAB3IL1) were incorporated into subsequent KEGG and GO analyses. Functional assays confirmed that silencing PTPN12, YTHDC2 and MAPKAPK3, or overexpressing GPX3, RASA3 and TSPAN4, significantly suppressed DCIS cell invasion. These DEGs were linked to immune functions, such as antigen processing and presentation and the tumor microenvironment (TME), and they showed associations with dendritic cell activation differences. Conclusions: Thirteen genes were associated with DCIS progression, and six genes were validated in the cell experiments. KEGG and GO analyses highlight TME’s role in early breast cancer, enhancing understanding of DCIS occurrence and aiding identification of high-risk tumors. Full article

HIV infection is known to increase the risk for cardiovascular disease (CVD). Although almost 400 single-nucleotide polymorphisms (SNPs) are significantly associated with CAD alone, a subtype of CVD, the functions of most of these risk loci are unclear. Here, we investigated the impact of genetic variants/SNPs on the expression of nearby genes as potential cis expression quantitative trait loci (cis-eQTLs). We investigated peripheral blood mononuclear cells (PBMCs) from 31 participants in the Women’s Interagency HIV Study (WIHS) using genotyping, single-cell (sc)RNA-seq, and CITE-seq. We found 187 statistically significant sc-eQTLs (single-cell eQTLs). In total, 160 were specific for just one immune cell type. We found a set of 3 sc-eQTLs impacting expression of IFNGR1 in CD4+ T cells at the mRNA and protein level as detected by flow cytometry. Two other sc-eQTLs representing one locus impact IFNG expression in CD8+ T cells, one of the primary sources of this cytokine. The sc-eQTLs impacting IFNG were associated with Th1 (T-helper1) gene expression patterns in CD4+ T cells in this cohort. These data suggest that some individuals are genetically predisposed to greater levels of Th1 polarization, which is known to be associated with atherosclerosis. Full article

The causal contributions of specific mitochondrial genes to common pain phenotypes remain unclear. We employed a multi-omics Mendelian randomization (SMR) approach, integrating QTL data (expression, methylation, protein) for mitochondrial genes with GWAS summary statistics for seven pain phenotypes. We identified 18 candidate genes with robust SMR associations across omics layers. However, strong colocalization evidence (PP.H4 > 0.7) was largely absent, pointing towards complex genetic architectures. A notable exception was a strong signal for a shared causal variant found at the methylation level for the MCL1 gene in hip pain (PP.H4 = 0.962), nominating it as a high-confidence candidate. Additionally, genetically predicted higher protein levels of Glycine amidinotransferase (GATM) showed consistent protective associations with neck or shoulder, back, and knee pain. This study provides novel evidence for mitochondrial gene regulation in pain, highlighting the GATM pathway as protective and identifying MCL1 methylation as a potential causal mechanism in hip pain. Full article

Considering the importance of carotenoids in the human diet, their enhancement is a key trait in current breeding programs. This study assessed lutein, zeaxanthin, α-carotene, and β-carotene levels in the flesh of mature fruits from 257 global C. pepo accessions. Lutein and β-carotene were the most prevalent, with top accessions identified for each carotenoid. A panel of 120 accessions with reliable carotenoid contents and genetic diversity was analyzed using 23,111 GBS-generated SNPs in genome-wide association studies (GWAS). Three genomic regions (qtl1, qtl3, and qtl13) on chromosomes 1, 3, and 13 were significantly linked to carotenoid levels, with alternative alleles increasing the carotenoid content, leading to yellowish–orange flesh. Seven candidate genes were identified: CpTIC56, CpHSHP70, and CpPDL8, which regulate carotenoid biosynthesis in chloroplasts; CpSPX and CpPHO1, associated with phosphate homeostasis and carotenoid buildup; CpMYB106, co-expressed with carotenoid biosynthesis genes; and a CpPPR RNA-binding protein. RNA-seq data from yellow- and white-fleshed fruits supported their involvement in carotenoid accumulation. These results improve our understanding of the genetic control of carotenoid buildup in C. pepo fruit, supporting breeding efforts for improved nutritional quality. Full article

Alkaline stress, driven by high pH and carbonate accumulation, results in severe physiological damage in plants. While the molecular mechanisms underlying alkaline tolerance have been partially elucidated in many crops, they remain largely unexplored in wheat. We hypothesize that alkaline stress tolerance in wheat is genotype-dependent. This study employed an integrated multi-omics approach to assess alkaline stress responses, combining genome-wide association study (GWAS) and RNA-seq analyses. Systematic phenotyping revealed severe alkaline stress-induced root architecture remodeling—with 57% and 73% length reductions after 1- and 3-day treatments, respectively—across 258 accessions. Analysis of the GWAS results identified nine significant alkaline tolerance QTLs on chromosomes 1A, 3B, 3D, 4A, and 5B, along with 285 associated candidate genes. Using contrasting genotypes—Dingxi 38 (tolerant) and TDP.D-27 (sensitive)—as experimental materials, physiological analyses demonstrated that root elongation was less inhibited in Dingxi 38 under alkaline stress compared to TDP.D-27, with superior root integrity observed in the tolerant genotype. Concurrently, Dingxi 38 exhibited enhanced reactive oxygen species (ROS) scavenging capacity. Subsequent RNA-seq analysis identified differentially expressed genes (DEGs) involved in ion homeostasis, oxidative defense, and cell wall remodeling. Integrated GWAS and RNA-seq analyses allowed for the identification of seven high-confidence candidate genes, including transcription factors (MYB38, bHLH148), metabolic regulators (ATP-PFK3), and transporters (OCT7), elucidating a mechanistic basis for adaptation to alkaline conditions. These findings advance our understanding of alkaline tolerance in wheat and provide candidate targets for molecular breeding of saline- and alkaline-tolerant crops. Full article

Background: Host genetic factors significantly influence individual susceptibility to severe COVID-19, potentially explaining the observed disparities in clinical outcomes across populations. One of the key effectors in innate immunity and antiviral defense is the CD209 gene. This study explored the potential correlation of the CD209 gene SNP rs2287886 with diverse COVID-19 patient outcomes. Materials and Methods: A total of 176 patients (87 in the moderate group and 89 in the severe/critical/death group) were included in the study. Genotyping of patients was performed using the qPCR methodology, through the TAQMAN system. The results were analyzed adopting a significance level of p < 0.05. Results: The GG genotype (compared to AG + AA) and the G allele (compared to the A allele) of the rs2287886 SNP were significantly associated with an increased severity of COVID-19 (p = 0.0005 and p < 0.0001, respectively). The G allele was more frequent in individuals with more severe clinical outcomes (49.43% vs. 25.28%). Furthermore, expression quantitative trait loci (eQTL) analysis indicated that the GG genotype of rs2287886 is associated with higher CD209 gene expression. Furthermore, the observed interaction analysis suggests that the interactions between CD209 and its associated proteins may play a role in modulating the immune response. Conclusions: Our findings suggest that Brazilian patients homozygous for the GG genotype of the rs2287886 polymorphism in the CD209 gene may be at increased risk of severe COVID-19 in the Brazilian population and may act as a potential prognostic marker of disease severity. Full article

Dickeya solani causes soft rot in potato (Solanum tuberosum L.) tubers. We used bulk RNA-seq to compare the early transcriptional responses of the diploid F₁ genotypes from the mapping population that varied in tuber resistance to D. solani. RNA was collected from wounded tubers inoculated with D. solani (B), wounded tubers treated with sterile water (W), and non-treated tubers (NT) at 8, 24, and 48 hours post-inoculation (hpi). The largest transcriptional divergence between resistant (R) and susceptible (S) genotypes occurred at 8 hpi, with R tubers showing stronger induction of phenylpropanoid biosynthesis, phenylalanine and tyrosine metabolism, amino sugar and nucleotide sugar metabolism, isoquinoline alkaloid biosynthesis, and glutathione metabolism. Phenylpropanoid biosynthesis was dominant in R tubers, in 17 differentially expressed genes (DEGs), consistent with rapid suberin and lignin deposition as a physical barrier. RT-qPCR of nine defence-related genes corroborated the RNA-seq trends. The suberisation-associated anionic peroxidase POPA was located within a QTL for D. solani resistance on chromosome II, supporting its role as a candidate for future functional studies. This is the first transcriptome-based comparison of R and S potato genotypes challenged with D. solani, providing candidate pathways and genes that may guide future molecular breeding once their roles are validated. Full article